Document Detail


Vitamin B-6 restriction impairs fatty acid synthesis in cultured human hepatoma (HepG2) cells.
MedLine Citation:
PMID:  23211517     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vitamin B-6 deficiency has been reported to alter n-6 and n-3 fatty acid profiles in plasma and tissue lipids; however, the mechanisms underlying such metabolic changes remain unclear. The objective of this study was to determine the effects of vitamin B-6 restriction on fatty acid profiles and fatty acid synthesis in HepG2 cells. Cells were cultured for 6 wk in media with four different vitamin B-6 concentrations (10, 20, 50, and 2,000 nM added pyridoxal, representing deficient, marginal, adequate, and supraphysiological conditions) that induced a range of steady-state cellular concentrations of pyridoxal phosphate. Total cellular lipid content was greatest in the deficient (10 nM pyridoxal) medium. The percentage of arachidonic acid and the ratio of arachidonic acid to linoleic acid in the total lipid fraction were ~15% lower in vitamin B-6-restricted cells, which suggests that vitamin B-6 restriction affects n-6 fatty acid interconversions. Metabolic flux studies indicated significantly lower fractional synthesis rate of oleic acid and arachidonic acid at 10, 20, and 50 nM pyridoxal, whereas that of eicosapentaenoic acid was lower in the cells cultured in 10 nM pyridoxal. Additionally, relative mRNA expressions of Δ5 and Δ6 desaturases were 40-50% lower in vitamin B-6-restricted cells. Overall, these findings suggest that vitamin B-6 restriction alters unsaturated fatty acid synthesis, particularly n-6 and n-3 polyunsaturated fatty acid synthesis. These results and observations of changes in human plasma fatty acid profiles caused by vitamin B-6 restriction suggest a mechanism by which vitamin B-6 inadequacy influences the cardiovascular risk.
Authors:
Mei Zhao; Maria A Ralat; Vanessa da Silva; Timothy J Garrett; Stephan Melnyk; S Jill James; Jesse F Gregory
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-04
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  304     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-18     Completed Date:  2013-04-05     Revised Date:  2014-02-18    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E342-51     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Hepatocellular / metabolism
Cell Membrane / metabolism*
Down-Regulation*
Fatty Acid Desaturases / genetics,  metabolism*
Fatty Acids / metabolism*
Fatty Acids, Omega-3 / metabolism
Fatty Acids, Omega-6 / metabolism
Hep G2 Cells
Hepatocytes / metabolism*
Humans
Intracellular Membranes / metabolism
Kinetics
Linoleoyl-CoA Desaturase / genetics,  metabolism*
Liver Neoplasms / metabolism
Neoplasm Proteins / genetics,  metabolism
Osmolar Concentration
Pyridoxal / metabolism
Pyridoxal Phosphate / metabolism
RNA, Messenger / metabolism
Vitamin B 6 Deficiency / metabolism*
Grant Support
ID/Acronym/Agency:
1UL1RR-029890/RR/NCRR NIH HHS; R01 DK072398/DK/NIDDK NIH HHS; R01DK-072398/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Fatty Acids, Omega-3; 0/Fatty Acids, Omega-6; 0/Neoplasm Proteins; 0/RNA, Messenger; 3THM379K8A/Pyridoxal; 5V5IOJ8338/Pyridoxal Phosphate; EC 1.14.19.-/Fatty Acid Desaturases; EC 1.14.19.3/Linoleoyl-CoA Desaturase; EC 1.14.99.-/delta-5 fatty acid desaturase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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